Metal-Free Radical Oxidative Cyclization of o-Azidoaryl Acetylenic Ketones with Sulfinic Acids To Access Sulfone-Containing 4-Quinolones

Article abstract of DOI:10.1021/acs.joc.6b01847

A novel one-pot synthesis of sulfone-containing 4-quinolones with easily available sulfinic acids as sulfonylating precursors is described. This reaction is characterized by mild reaction conditions, high functional-group tolerance and amenability to gram-scale synthesis.

Full text of DOI:10.1021/acs.joc.6b01847

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Article
Metal-free radical Oxidative Cyclization of o-Azidoaryl Acetylenic
Ketones with Sulfinic acids to Access Sulfone-Containing 4-Quinolones
Nengneng Zhou, Zhongfei Yan, Honglin Zhang, Zhongkai Wu, and Chengjian Zhu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b01847 • Publication Date (Web): 22 Nov 2016
Downloaded from http://pubs.acs.org on November 23, 2016
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The Journal of Organic Chemistry
Metal-free radical Oxidative Cyclization of o-Azidoaryl Acety-
lenic Ketones with Sulfinic acids to Access Sulfone-Containing 4-
Quinolones
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Nengneng Zhou,a Zhongfei Yan,a Honglin Zhang,a Zhongkai Wua and Chengjian Zhua,b*
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aState Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University,
Nanjing 210093, P. R. China.
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bShanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai,200032, China
cjzhu@nju.edu.cn
RECEIVED DATE (to be automatically inserted after your manuscript is accepted if required according to the
journal that you are submitting your paper to)
ABSTRACT
A novel one-pot synthesis of sulfone-containing 4-quinolones with easily available sulfinic acids as sulfonylating
precursors is described. This reaction is characterized by mild reaction conditions, high functional-group tolerance and
amenability to gram-scale synthesis.
INTRODUCTION
4-Quinolone skeleton has been widely found in natural products and pharmaceuticals1 and biologically active
molecules for antimitotic,2 antimalarial,3 anticancer,4 xanthine oxidase, and cathepsins inhibitory activities.5
Therefore, the efficient synthesis of 4-quinolones has attracted interest of chemists and pharmacologists.6 In re-
cent decades, many methods have been established in the construction of 4-quinolone framework. As is well
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known, classical methods such as Niementowski, Conrad−Limpet,8 and Camps cyclizations9 are based on cy-
clocondensation, which suffered from harsh reaction conditions and unavailability of starting materials. Recently,
transition-metal-catalyzed synthesis of 4-quinolone derivatives has become a useful strategy.10 Among selected
elegant examples, Xu group employed a Pd-catalyzed addition reactions of o-azidoaryl acetylenic ketones and
primary amines to provide 4-quinolones in 201010f (Scheme 1, eq 1). Then, Helaja reported a gold-catalyzed in-
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termolecular addition of amine to alkynes to form various 4-quinolones10h (Scheme 1, eq 2). Recently, Larhed
described a Pd-catalyzed synthesis of 4-quinolones from 2-iodoanilines, alkynes and molybdenum hexacarbon-
yl10g (Scheme 1, eq 3). Although significant achievements have been made, a milder and more efficient method
for the synthesis of functionalized 4-quinolones is still in demand.
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Because of the unique chemical properties and biological activities of sulfones, construction of sulfone-
containing molecules has an important effect on the design of lead compounds in agrochemicals and materials
chemistry.[11] Consequently, a large number of methods for the incorporation of sulfonyl group have been exten-
sively researched in the past decades.12 Arylsulfinic acids are versatile, easy to handle, and have been widely used
as sulfonylation reagents for the preparation of organosulfones.13 However, to our best knowledge, method to
construction of molecules bearing both a 4-quinolone motif and a sulfonyl group was rarely reported.14 Based on
the importance of the sulfonyl group and our continuing interest in the synthesis of heterocyclic scaffolds frame-
works,15 herein, we report a novel tert-butyl hydroperoxide (TBHP) initiated difunctionalization of alkynes with
sulfinic acids via C–N and C–S bond formation for the synthesis of 3-sulfonated 4-quinolones under metal-free
conditions (Scheme 1, eq 4).
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Scheme 1. Construction of 4-quinolones derivatives
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RESULTS AND DISCUSSION
Initially, the reaction of 1-(2-azidophenyl)-3-phenylprop-2-yn-1-one (1a) with p-tolylsulfinic acid (2a) in the
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presence of the radical initiator azodiisibutyronitrile (AIBN) was examined. To our delight, the desired 2-phenyl-
3-tosylquinolin-4(1H)-one (3aa) was obtained in 72% yield (Table 1, entry 1). After sceening of a series of radi-
cal initiators such as di-tert-butyl peroxide (DTBP), tert-butyl hydroperoxide (TBHP) and tert-butyl peroxyben-
zoate (TBPB), tert-butyl hydroperoxide (TBHP) was found to be the most efficient (Table 1, entry 3). By increas-
ing the amount of TBHP to 0.4 equiv, the yield of 3aa was increased to 90% (Table 1, entry 6). Among the sol-
vents screened such as EtOH, toluene, DMF, DMSO and DMA, CH3CN was proved to be the best choice for this
reaction (Table 1, entries 7-11). There is no influence on reaction yield when the amount of TBHP was further
increased (Table 1, entries 12-13). In the following study, 2 equiv was found to be the ideal amount of p-
tolylsulfinic acid 2a (Table 1, entries 14-15). Consequently, the optimum reaction conditions were determined to
be TBHP (0.4 equiv) in CH3CN at 80 °C under Ar for 0.5 h (Table 1, entry 6).
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Table 1. Optimization of reaction condition a
Entry
1
initiator
t (oC)
80
Solvent
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
EtOH
Yield(%)b
AIBN(0.2 equiv)
TBHP(0.2 equiv)
TBHP(0.2 equiv)
DTBP(0.2 equiv)
TBPB(0.2 equiv)
TBHP(0.4 equiv)
TBHP(0.4 equiv)
TBHP(0.4 equiv)
TBHP(0.4 equiv)
TBHP(0.4 equiv)
TBHP(0.4 equiv)
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67
76
62
65
90
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83
80
91
2c
80
3
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4
100
80
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80
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80
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80
toluene
DMF
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80
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11
80
DMSO
DMA
80
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13
TBHP(0.5 equiv)
TBHP(0.6 equiv)
TBHP(0.4 equiv)
TBHP(0.4 equiv)
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80
80
80
MeCN
MeCN
MeCN
MeCN
87
0
14d
15e
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aAll reactions were carried out by using 1a (0.2 mmol), 2a (2.0 equiv), TBHP (5−6 M in decane), and solvent (1 mL) under argon (1 atm)
and stirred for 0.5 h, except as noted. bIsolated yield. cTBHP (70% aqueous). d2a (1.2 equiv) was used. e2a (1.5 equiv) was used.
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With the optimized conditions in hand (Table 1, entry 6), we then studied the scope of the cyclization of p-
tolylsulfinic acid with a series of o-azidoaryl acetylenic ketones, as shown in table 2. First, we examined the ef-
fect of the substitution pattern on the aryl ring attached to the triple bond. Both electron-donating (1b-1d) and
electron-withdrawing (1e-1g) groups on the aromatic ring produced the corresponding 3-tosylquinolin-4(1H)-
ones in good yields. The structure of 3fa was confirmed by single-crystal X-ray analysis (see the Supporting In-
formation). Other substitution pattern of the aryl ring directly bound to the triple bond such as 4-phenyl and 4-
ethyl were also tolerated well in this process and smoothly converted into products 3ha and 3ia in 92% and 94%
yields, respectively. Then, functional groups on the aromatic ring of the arylazide moiety such as chloro and bro-
mo groups were examined and gave the corresponding products 3ja-3la in 87-93% yields. When benzene rings
were both substituted, the desired product 3ma was formed in 91% yield. In addition, a substrate with thiophene
attached to the triple bond (1n) could also provide the expected product in 96% yield. Unfortunately, there was no
desired product detected when R’ in 1 was an atom H or an alkyl group n-C4H9. To further show the practical ap-
plication of this method, 1-(2-azidophenyl)-3-phenylprop-2-yn-1-one (1a, 5 mmol) was employed in a gram-scale
reaction and delivered 3aa in 84% yield.
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Table 2. Synthesis of 2-Aryl-3-Tosylquinolin-4(1H)-one Derivatives a
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a Reaction conditions: 1 (0.2 mmol), p-tolylsulfinic acid (2 equiv) and TBHP (0.4 equiv) in CH3CN (1 mL) at 80 °C under an argon atmos-
phere for 0.5 h. Yields are given for isolated products.
Next, the reactions of various sulfinic acids with 1-(2-azidophenyl)-3-phenylprop-2-yn-1-one 1a were exam-
ined (Table 3). We were pleased to find that benzenesulfinic acid was able to furnish the desired product, 2-
phenyl-3-(phenylsulfonyl) quinolin-4(1H)-one (3ab), in 88% yield. Gratifyingly, arylsulfinic acids 2, bearing ei-
ther electron-donating (MeO and tBu) or electron-withdrawing (Br) groups at the 2 or 4 positions of the aromatic
ring were compatible with the optimized conditions (3ac-3af). However, 2-bromobenzenesulfinic acid reacted
with 1a to afford 3ad in 67% yield, suggesting that the reaction was influenced by the steric effect. Moreover, 2-
naphthylsulfinic acid was also suitable for this conversion to give the corresponding desired product 3ag in good
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yield (80%). Unfortunately, the aliphatic sulfinic acid, such as methanesulfinic acid, failed to react under the op-
timized reaction conditions.
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Table 3 Scope of Sulfinic Acids a
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a Reaction conditions: 1a (0.2 mmol), 2 (2 equiv) and TBHP (0.4 equiv) in CH3CN (1 mL) at 80 °C under an argon atmosphere for 0.5 h.
Yields are given for isolated products.
4-Quinolone skeleton is a common-structure unit in organic synthesis. Further transformations of 4-quinolone
can be used to prepare many important potentially bioactive molecules or important organic synthetic intermedi-
ates. As exemplified in Scheme 2, 3aa can be easily converted to 1-methyl-2-phenyl-3-tosylquinolin-4(1H)-one (4)
in 86% yield when reacted with iodomethane and NaH.
Scheme 2. Follow-up transformation of 3aa
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In order to understand the reaction mechanism, radical-trapping experiments were carried out. When the reac-
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tion was conducted with a radical scavenger 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) or 2,6-di-tert-butyl-
4-methylphenol (BHT), the reaction was substantially inhibited, suggesting that the reaction involves a radical
process. On the base of the above-mentioned experiments and literature reports13e, two possible pathways may be
involved in this reaction: a) radical chain propagation mechanism; b) radical-radical coupling mechanism. In path
a, the initiate step begin with the reaction of sulfinic acid 2 with TBHP to generate the corresponding I, which
could be resonating with sulfonyl radical II. Subsequently, the sulfonyl radical II adds to the alkynyl moiety of
substrate 1a to afford the vinyl radical III, which undergoes rapid intramolecular cyclization to give the N-radical
intermediate IV. The N-radical IV could undergo hydrogen abstraction (HAT) from sulfinic acid to give the de-
sired product 3 and regenerate radical II (propagation step). The radical-radical coupling pathway (path b) may
be also possible in this reaction. First, nitrene intermediate V formed from substrate 1a by releasing N2 under
heating condition. Then, the nitrene intermediate V reacts with tert-butoxy radical to generate the intermediate
VI,16 which immediately undergoes intramolecular cyclization to yield the intermediate VII. The intermediate
VII goes through cross-coupling with sulfonyl radical II to yield the intermediate VIII, which then hydrolyzed
into product 3.
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Scheme 3. Plausible mechanism
CONCLUSION
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In summary, we have disclosed a method for TBHP-initiated cascade of S-central radical addition and cycliza-
tion of o-azidoaryl acetylenic ketones with sulfinic acids, providing direct access to various 3-sulfonated 4-
quinolones. This new method is a mild, environmentally benign system and applicable to gram scale synthesis.
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EXPERIMENTAL SECTION
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General Information: All reactions were carried out under Ar atmosphere unless otherwise noted. All catalysts and
solvents were obtained from commercial suppliers. Reactions were monitored by TLC on silica gel plates (GF254),
and the analytical thin-layer chromatography (TLC) was performed on precoated, glass-backed silica gel plates. Sulfin-
ic acids 2a−2g were synthesized according to the literature.17 1H NMR, 13C NMR spectra and 19F NMR spectra were
recorded on 400 MHz spectrometer at room temperature. Chemical shifts (δ) are reported in ppm downfield from tet-
ramethylsilane. High resolution mass spectra were obtained on a high–resolution mass spectrometer in the ESI mode.
General Procedure for the Synthesis of o-azidoaryl acetylenic ketones 1a-1i, 1n-1p.18
(1) Sodium azide (0.72 g, 11 mmol) was added to a stirring solution of 2-nitrobenzaldehydes (0.8 g, 5 mmol) in
HMPA (15 mL) at 0 °C. The water bath was allowed to warm to ambient temperature and monitored by TLC. After the
reaction was finished, the mixture extracted with methyl tert-butyl ether. The organic phase was washed with water,
concentrated in vacuo, dried over Na2SO4. The solvent was removed under vacuum, and the residue was purified by
flash column chromatography on silica gel using petroleum ether-ethyl acetate mixture as eluent (96:4 v/v).
(2) To a solution of phenylacetylene (1.1 equiv) in dry THF (15 mL) at 0°C was added n-BuLi (2.5 M solution in
hexane, 1.1 equiv) dropwise. The reaction mixture was stirred at -78°C for 30 min. A solution of ortho-
azidobenzaldehydes (1 equiv) in THF (10 mL) was then added slowly and stirred for 3 h. Saturated ammonium chlo-
ride was added in the mixture at room temperature. The THF layer was separated and the aqueous one was further ex-
tracted with Et2O. The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated
in vacuo. The crude product was directly used in the next step without further purification.
(3) To a solution of the crude o-azidoaryl acetylenic alcohols in Et2O (20 ml), the Jones’ reagent (4 mL) was added
dropwise slowly at 0 °C for 0.5 h. The mixture was allowed to warm to room temperature and stirred 1 h. After com-
pletion, the reaction was quenched with H2O and extracted with Et2O. The organic extracts were washed with brine,
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dried and concentrated in vacuo. Purification of the residue was performed by silica gel column chromatography using
petroleum ether-ethyl acetate mixture as eluent (40:1 v/v) to give the pure product.
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1-(2-azidophenyl)-3-phenylprop-2-yn-1-one (1a).Yellow solid; (0.753g, 61%); mp: 62–65 C; Rf = 0.51 (hex-
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anes/ethyl acetate 40:1);1H NMR (400 MHz, CDCl3): δ = 8.17 (dd, J = 8.0 Hz, J = 1.6 Hz, 1H), 7.67-7.65 (m, 2H),
7.62-7.58 (m, 1H), 7.51-7.46 (m, 1H), 7.44-7.40 (m, 2H), 7.30-7.25 (m, 2H) ppm; 13C NMR (100.6 MHz, CDCl3): δ
176.1, 140.2, 134.2, 133.1, 130.8, 128.9, 128.7, 124.6, 120.1, 93.3, 88.3 ppm. MS m/z (relative intensity, %): 247 (0.9),
219 (20.6), 218 (6.4), 217 (100), 216 (16.2), 198 (21.5), 196 (24.8), 182 (14.5), 154 (10.2), 126 (32.1).
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1-(2-azidophenyl)-3-(p-tolyl)prop-2-yn-1-one (1b). Yellow solid; (0.717g, 55%); mp: 76–78 C; Rf = 0.52 (hex-
anes/ethyl acetate 40:1);1H NMR (400 MHz, CDCl3): δ = 8.16 (dd, J = 8.0 Hz, J = 1.6 Hz, 1H), 7.61-7.54 (m, 3H),
7.29-7.21 (m, 4H), 2.40 (s, 3H) ppm; 13C NMR (100.6 MHz, CDCl3): δ 176.1, 141.6, 140.1, 134.1, 133.1, 133.0, 129.5,
129.0, 124.5, 120.1,117.0, 94.1, 88.2, 21.8 ppm. MS m/z (relative intensity, %): 261 (5.8), 246 (20.6), 245 (17.4), 244
(100.0), 230 (16.2), 216 (26.5), 202 (14.8), 184 (7.5), 168 (30.2), 78 (22.1).
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1-(2-azidophenyl)-3-(4-methoxyphenyl)prop-2-yn-1-one (1c). Yellow solid; (0.803g, 58%); mp: 78–81 C; Rf = 0.51
(hexanes/ethyl acetate 40:1); 1H NMR (400 MHz, CDCl3): δ = 8.15 (dd, J = 8.0 Hz, J = 1.6 Hz, 1H), 7.63-7.56 (m, 3H),
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7.30-7.25 (m, 2H), 6.93 (d, J = 8.8 Hz, 2H), 3.86 (s, 3H) ppm; C NMR (100.6 MHz, CDCl3): δ 176.1, 161.8, 140.0,
135.2, 134.0, 132.9, 129.2, 124.5, 120.1, 114.4, 111.9, 94.6, 88.4, 55.4 ppm. MS m/z (relative intensity, %): 277 (14.5),
262 (20.6), 249 (14.6), 248 (100), 247 (16.2), 232 (26.5), 218 (14.8), 202 (14.5), 184 (20.2), 92 (22.1).
o
1-(2-azidophenyl)-3-(3-methoxyphenyl)prop-2-yn-1-one (1d). Yellow solid; (0.623g, 45%); mp: 80–84 C; Rf = 0.60
(hexanes/ethyl acetate 40:1);1H NMR (400 MHz, CDCl3): δ = 8.17 (dd, J = 8.0 Hz, J = 1.6 Hz, 1H), 7.62-7.58 (m, 1H),
7.34-7.24 (m, 4H), 7.16 (d, J = 0.8 Hz, 1H),7.04-7.02 (m, 1H), 3.83 (s, 3H) ppm; 13C NMR (100.6 MHz, CDCl3): δ
176.0, 159.4, 140.2, 134.2, 133.1, 129.7, 128.8, 125.5, 124.5,121.0, 120.1, 117.6, 117.5, 93.2, 87.9, 55.4 ppm. MS m/z
(relative intensity, %): 277 (6.5), 262 (30.6), 246 (100.0), 235 (60.6), 244 (16.2), 230 (6.5), 216 (14.8), 186 (34.5), 172
(7.2), 86 (32.1).
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1-(2-azidophenyl)-3-(4-fluorophenyl)prop-2-yn-1-one (1e). Yellow solid; (0.742g, 56%); mp: 82–84 C; Rf = 0.53
(hexanes/ethyl acetate 40:1); 1H NMR (400 MHz, CDCl3): δ = 8.14 (dd, J = 8.0 Hz, J = 1.6 Hz, 1H), 7.68-7.64 (m, 2H),
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7.63-7.58 (m, 1H), 7.30-7.25 (m, 2H),7.15-7.09 (m, 2H) ppm; C NMR (100.6 MHz, CDCl3): δ 175.9, 164.1 (d, J =
252.1 Hz), 140.2, 135.4, 135.3, 134.3, 133.0, 128.8, 124.6, 116.2 (d, J = 28.2 Hz), 92.3, 88.3 ppm. 19F NMR (376 MHz,
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CDCl3): -105.95; MS m/z (relative intensity, %): 265 (4.5), 246 (20.6), 245 (100.0), 231 (60.6), 217 (26.2), 203 (26.5),
185 (24.8), 161 (4.5), 60 (22.1).
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1-(2-azidophenyl)-3-(4-chlorophenyl)prop-2-yn-1-one (1f). Yellow solid; (0.871, 62%); mp: 86–88 C; Rf = 0.52
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(hexanes/ethyl acetate 40:1); 1H NMR (400 MHz, CDCl3): δ = 8.14 (dd, J = 8.0 Hz, J = 1.6 Hz, 1H), 7.62-7.56 (m, 3H),
7.41-7.39 (m, 2H), 7.30-7.25 (m, 2H) ppm; 13C NMR (100.6 MHz, CDCl3): δ 175.8, 140.3, 137.2, 134.4, 134.2, 133.0,
129.1, 128.7, 124.6, 120.1, 118.6, 91.8, 89.0 ppm. MS m/z (relative intensity, %): 281 (18.5), 245 (20.6), 244 (100.0),
243 (60.6), 229 (16.2), 215 (26.5), 201 (14.8), 185 (14.5), 169(20.2), 154 (22.1).
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1-(2-azidophenyl)-3-(4-bromophenyl)prop-2-yn-1-one (1g). Yellow solid; (1.05g, 65%); mp: 85–88 C; Rf = 0.51
(hexanes/ethyl acetate 40:1); 1H NMR (400 MHz, CDCl3): δ = 8.14 (dd, J = 8.0 Hz, J = 1.6 Hz, 1H), 7.61-7.50 (m, 5H),
7.30-7.25 (m, 2H), ppm; 13C NMR (100.6 MHz, CDCl3): δ 175.8, 140.3, 134.4, 134.3, 133.0, 132.1, 128.7, 125.6,
124.6, 120.1, 119.1, 91.9, 89.1 ppm. MS m/z (relative intensity, %): 326 (2.9), 324 (3.2), 298 (4.7), 296 (4.6), 228
(14.7), 227 (100.0), 225 (5.4), 201 (14.5), 200 (20.2), 101 (22.1).
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1-(2-azidophenyl)-3-(4-ethylphenyl)prop-2-yn-1-one (1h). Yellow solid; (0.866g, 63%); mp: 81–84 C; Rf = 0.57
(hexanes/ethyl acetate 40:1); 1H NMR (400 MHz, CDCl3): δ = 8.17 (dd, J = 8.0 Hz, J = 1.6 Hz, 1H), 7.59-7.57 (m, 3H),
7.30-7.24 (m, 4H), 2.70 (q, J = 14.8 Hz, J = 7.6 Hz, 2H), 1.26 (t, J = 7.6 Hz, 3H) ppm; 13C NMR (100.6 MHz, CDCl3):
δ 176.2, 147.8, 140.1, 134.1, 133.2, 133.1, 129.0, 128.3, 124.5, 120.1, 117.2, 94.1, 88.2, 29.0, 15.1 ppm. MS m/z (rela-
tive intensity, %): 275 (24.5), 248 (20.6), 247 (100.0), 246 (60.6), 245 (16.2), 244 (26.5), 234 (14.8), 220 (14.5), 219
(20.2), 170 (22.1).
3-([1,1'-biphenyl]-4-yl)-1-(2-azidophenyl)prop-2-yn-1-one (1i). Yellow solid; (1.06g, 66%); mp: 87–91 oC; Rf = 0.54
(hexanes/ethyl acetate 40:1); 1H NMR (400 MHz, CDCl3): δ = 8.17 (dd, J = 8.0 Hz, J = 1.6 Hz, 1H), 7.70-7.68 (m, 2H),
7.62-7.57 (m, 5H), 7.46-7.42 (m, 2H), 7.38-7.35 (m, 1H), 7.27-7.24 (m, 1H) ppm; 13C NMR (100.6 MHz, CDCl3): δ
175.9, 143.5, 140.0, 139.5, 134.1, 133.5, 133.0, 128.9, 128.7, 128.1, 127.2, 127.0, 124.5, 120.1, 118.7, 93.3, 88.9 ppm.
MS m/z (relative intensity, %): 323 (18.5), 296 (20.6), 295 (100.0), 294 (60.6), 293 (16.2), 292 (26.5), 282 (14.8), 268
(14.5), 267 (20.2), 218(22.1).
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1-(2-azidophenyl)-3-(thiophen-2-yl)prop-2-yn-1-one (1n). Yellow solid; (0.518g, 41%); mp: 37–39 C; Rf = 0.62
(hexanes/ethyl acetate 40:1)1H NMR (400 MHz, CDCl3): δ = 8.10 (dd, J = 7.6 Hz, J = 1.6 Hz, 1H), 7.62-7.53 (m, 3H),
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7.30-7.25 (m, 2H), 7.10 (dd, J = 5.2 Hz, J = 4.0 Hz, 1H) ppm; C NMR (100.6 MHz, CDCl3): δ 175.4, 140.2, 136.8,
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134.2, 132.7, 131.9, 128.7, 127.8, 124.6, 120.1, 120.0, 93.3, 87.5 ppm. MS m/z (relative intensity, %): 253 (18.6), 226
(12.9), 225 (64.2), 224 (100.0), 198 (9.2), 197 (8.0), 181 (10.4), 180 (10.1), 154 (6.4), 113 (9.8).
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1-(2-azidophenyl)hept-2-yn-1-one (1o). Yellow oil; (0.579g, 51%); Rf = 0.46 (hexanes/ethyl acetate 40:1);1H NMR
(400 MHz, CDCl3): δ = 8.08 (dd, J = 7.6 Hz, J = 1.6 Hz, 1H), 7.56-7.54 (m, 1H), 7.27-7.21 (m, 2H), 2.48 (t, J = 7.6 Hz,
2H), 1.68-1.61 (m, 2H), 1.54-1.45 (m, 2H), 0.96 (t, J = 7.6 Hz, 3H) ppm; 13C NMR (100.6 MHz, CDCl3): δ 176.4,
140.0, 133.9, 133.2, 129.0, 124.4, 120.1, 97.2, 81.1, 29.7, 22.0, 19.0, 13.5 ppm. MS m/z (relative intensity, %): 227
(9.5), 200 (20.6), 199 (100.0), 198 (60.6), 197 (40.4), 196 (20.3), 180 (16.2), 165(50.7), 154(22.1), 128(27.1), 113
(12.8).
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1-(2-azidophenyl)prop-2-yn-1-one (1p). Yellow solid; (0.41g, 48%);mp: 41–42 C; Rf = 0.51 (hexanes/ethyl acetate
40:1)1H NMR (400 MHz, CDCl3): δ = 8.15 (dd, J = 7.6 Hz, J = 1.6 Hz, 1H), 7.62-7.58 (m, 1H), 7.27-7.21 (dd, J = 16.0
Hz, J = 1.2 Hz, 2H), 3.48 (s, 1H) ppm; 13C NMR (100.6 MHz, CDCl3): δ 175.3, 140.0, 134.7, 133.7, 127.8, 124.5,
120.1, 81.2, 80.9 ppm. MS m/z (relative intensity, %): 171 (6.5), 157 (21.6), 144 (20.2), 143 (46.7), 142 (100),
114(35.1), 95(32.1), 77 (29.1).
[18]
General Procedure for the Synthesis of o-azidoaryl acetylenic ketones 1j-1m.
(1) Sodium azide (2.0 equiv)
was added to a stirring solution of ortho-fluorobenzaldehydes (1.0 equiv) in DMSO under argon. The reaction mixture
was stirred at 50 oC for 5-6 h. After the reaction was finished, the mixture poured into ice-cold water and acidified with
drops of concentrated HCl. It was then extracted with EtOAc, washed with water. The organic layer was dried over
MgSO4, and the solvent was removed under reduced pressure. The crude product was purified by flash column chro-
matography on silica gel using petroleum ether-ethyl acetate mixture as eluent (96:4 v/v). Step (2), (3) are same as
above-mentioned.
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1-(2-azido-5-chlorophenyl)-3-phenylprop-2-yn-1-one (1j).Yellow solid; (0.745g, 53%); mp: 76–79 C; Rf = 0.51
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(hexanes/ethyl acetate 40:1); H NMR (400 MHz, CDCl3): δ = 7.81 (d, J = 2.8 Hz, 1H), 7.67-7.65 (m, 2H), 7.53-7.48
(m, 1H), 7.45-7.26 (m, 2H), 7.25-7.22 (m, 2H) ppm; 13C NMR (100.6 MHz, CDCl3): δ 174.9, 136.8, 136.7, 133.2,
131.1, 129.9, 128.8, 124.7, 122.7, 121.8, 119.9, 93.4, 88.1 ppm. MS m/z (relative intensity, %): 281 (9.2), 236 (20.6),
235 (100.0), 234 (60.6), 233 (16.2), 232 (26.5), 208 (14.8), 206 (14.5), 204 (20.2), 180 (22.1).
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1-(2-azido-5-bromophenyl)-3-phenylprop-2-yn-1-one (1k).Yellow solid; (0.761g, 47%); mp: 88–91 C; Rf = 0.49
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(hexanes/ethyl acetate 40:1); H NMR (400 MHz, CDCl3): δ = 8.24 (d, J = 2.0 Hz, 1H), 7.70-7.65 (m, 3H), 7.53-7.48
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(m, 1H), 7.45-7.41 (m, 2H), 7.17 (d, J = 8.8 Hz, 2H) ppm; 13C NMR (100.6 MHz, CDCl3): δ 174.5, 139.3, 136.9, 135.4,
133.2, 131.1, 130.3, 128.7, 121.8, 119.9, 117.4, 94.4, 88.0 ppm. MS m/z (relative intensity, %): 326 (6.5), 324 (20.6),
298 (60.6), 296 (100), 260 (16.2), 258 (26.5), 246 (14.8), 244 (14.5), 230 (20.2), 180 (22.1).
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1-(2-azido-4-bromophenyl)-3-phenylprop-2-yn-1-one (1l).Yellow solid; (0.842g, 52%); mp: 91–95 C; Rf = 0.46
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(hexanes/ethyl acetate 40:1); H NMR (400 MHz, CDCl3): δ = 8.02 (d, J = 8.4 Hz, 1H), 7.66-7.63 (m, 2H), 7.51-7.47
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(m, 1H), 7.44-7.39 (m, 4H) ppm; 13C NMR (100.6 MHz, CDCl3): δ 175.0, 141.4, 134.1, 133.1, 131.0, 128.8, 128.7,
127.9, 127.6, 123.2, 119.9, 93.9, 88.1 ppm. MS m/z (relative intensity, %): 326 (18.5), 324 (3.2), 306 (4.7), 304(4.6),
224 (14.7), 223 (100.0), 221 (5.4), 207 (6.4), 206 (16.0), 103 (16.1).
1-(2-azido-4-bromophenyl)-3-(4-chlorophenyl)prop-2-yn-1-one (1m).Yellow solid; (0.972g, 54%); mp: 102–106 oC;
Rf = 0.45 (hexanes/ethyl acetate 40:1);1H NMR (400 MHz, CDCl3): δ = 8.00 (d, J = 8.4 Hz, 1H), 7.59-7.56 (m, 2H),
7.43-7.39 (m, 4H) ppm; 13C NMR (100.6 MHz, CDCl3): δ 174.8, 141.5, 137.5, 134.3, 134.1, 129.2, 129.0, 128.0, 127.5,
123.3, 118.4, 93.4, 88.8 ppm. MS m/z (relative intensity, %): 360 (20.7), 358 (20.6), 357 (100.0), 356 (20.6), 355
(16.2), 354 (36.5), 326 (14.8), 310 (24.5), 309 (20.2), 291 (12.1).
General procedure for sulfone-containing 4-quinolones 3: Schlenk tube (10 mL) was equipped with a magnetic stir
bar, o-azidoaryl acetylenic ketones 1 (0.2 mmol), sulfinic acids 2 (0.4 mmol, 2.0 equiv), CH3CN (1 ml). The flask was
evacuated and backfilled with Ar for 3 times. TBHP (0.08 mmol, 0.4 equiv, 5−6 M in decane) was added with syringe
under Ar. The tube was then sealed and the mixture was stirred for 0.5 h at 80 oC under Argon (1 atm). After the reac-
tion was finished, the solvent concentrated in vacuo and the residue was purified by chromatography on silica gel to
afford the corresponding products 3.
2-phenyl-3-tosylquinolin-4(1H)-one (3aa).White solid; (67.5 mg, 90%); mp: 272-276 oC; Rf = 0.34 (CH2Cl2 / methanol
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20:1); H NMR (400 MHz, DMSO-d6): δ = 12.38 (s, 1H), 8.02 (d, J = 7.6 Hz, 1H), 7.81-7.79 (m, 2H), 7.75-7.68 (m,
2H), 7.65-7.62 (m, 2H),7.58-7.55 (m, 3H), 7.43-7.39 (m, 1H), 7.31 (d, J = 8.0 Hz, 2H), 2.35 (s, 3H) ppm; 13C NMR
(100.6 MHz, DMSO-d6): δ 172.5, 154.7, 142.6, 140.1, 138.8, 134.2, 133.2, 129.5, 128.7, 128.4, 127.7, 127.6, 125.6,
125.2, 124.9, 119.0, 118.4, 21.0 ppm. ESI-HRMS: m/z Calcd for C22H17NO3S+H+: 376.1002, found 376.1004.
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2-(p-tolyl)-3-tosylquinolin-4(1H)-one (3ba).White solid; (70.8 mg, 91%); mp: 274-278 C; Rf = 0.36 (CH2Cl2 / metha-
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nol 20:1); H NMR (400 MHz, DMSO-d6): δ = 12.30 (s, 1H), 8.00 (d, J = 8.0 Hz, 1H), 7.79-7.77 (d, J = 8.0 Hz, 2H),
7.75-7.66 (m, 2H), 7.51 (d, J = 8.0 Hz, 2H), 7.43-7.35 (m, 3H), 7.31 (d, J = 8.4 Hz, 2H), 2.43 (s, 3H), 2.35 (s, 3H)
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ppm; 13C NMR (100.6 MHz, DMSO-d6): δ 172.5, 154.9, 142.6, 140.2, 139.1, 138.8, 133.2, 131.4, 128.7, 128.4, 128.2,
127.7, 125.6, 125.1, 124.9, 119.0, 118.4, 21.0 ppm. ESI-HRMS: m/z Calcd for C23H19NO3S+H+: 390.1158, found
390.1160.
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2-(4-methoxyphenyl)-3-tosylquinolin-4(1H)-one (3ca).White solid; (72.1 mg, 89%); mp: 280-283 oC; Rf = 0.40
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(CH2Cl2 / methanol 20:1); H NMR (400 MHz, DMSO-d6): δ = 12.27 (s, 1H), 7.99 (d, J = 7.6 Hz, 1H), 7.78-7.67 (m,
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4H), 7.58-7.55 (m, 2H),7.42-7.38 (m, 1H), 7.30 (d, J = 8.0 Hz, 2H), 7.12-7.10 (m, 2H), 3.86 (s, 3H), 2.35 (s, 3H) ppm;
13C NMR (100.6 MHz, DMSO-d6): δ 172.6, 160.4, 154.7, 142.6, 140.3, 138.8, 133.1, 130.2, 128.7, 127.7, 126.3,
125.6, 125.1, 124.9, 119.0, 118.4, 113.1, 55.3, 21.0 ppm. ESI-HRMS: m/z Calcd for C23H19NO4S+H+: 406.1108, found
406.1106.
2-(3-methoxyphenyl)-3-tosylquinolin-4(1H)-one (3da).White solid; (68.9 mg, 85%); mp: 275-278 oC; Rf = 0.36
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(CH2Cl2 / methanol 20:1); H NMR (400 MHz, DMSO-d6): δ = 12.38 (s, 1H), 8.00(d, J = 8.0 Hz, 1H), 7.81-7.76 (m,
2H), 7.74-7.68 (m, 2H),7.50-7.40 (m, 2H), 7.31 (d, J = 8.0 Hz, 2H), 7.22-7.10 (m, 3H), 3.85 (s, 3H), 2.36 (s, 3H) ppm;
13C NMR (100.6 MHz, DMSO-d6): δ 172.6, 158.5, 154.4, 142.7, 140.1, 138.8, 135.5, 133.2, 128.9, 128.7, 127.7,
125.6, 125.2, 124.9, 121.1, 119.1, 118.3, 114.9, 114.2, 55.3 21.0 ppm. ESI-HRMS: m/z Calcd for C23H19NO4S+H+:
406.1108, found 406.1104.
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2-(4-fluorophenyl)-3-tosylquinolin-4(1H)-one (3ea).White solid; (70 mg, 89%); mp: 282-286 C; Rf = 0.35 (CH2Cl2 /
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methanol 20:1); H NMR (400 MHz, DMSO-d6): δ = 12.41 (s, 1H), 8.01(d, J = 8.0 Hz, 1H), 7.79-7.66 (m, 6H), 7.44-
7.38 (m, 3H),7.31 (d, J = 8.0 Hz, 2H), 2.35 (s, 3H) ppm; 13C NMR (100.6 MHz, DMSO-d6): δ 172.6, 162.9 (d, J =
246.2Hz), 153.8, 142.7, 140.0, 138.7, 133.2, 130.9 (d, J = 10.2 Hz ), 130.5 (d, J = 5.2 Hz ), 128.7, 127.7, 125.7,
125.1(d, J = 23.2 Hz), 119.0, 118.5, 114.8, 114.6 ppm, 19F NMR (376 MHz, DMSO-d6): -111.92 ppm. ESI-HRMS:
m/z Calcd for C22H16FNO3S+H+: 394.0908, found 394.0910.
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2-(4-chlorophenyl)-3-tosylquinolin-4(1H)-one (3fa).White solid; (72 mg, 88%); mp: 272-276 C; Rf = 0.34 (CH2Cl2 /
methanol 20:1); 1H NMR (400 MHz, DMSO-d6): δ = 12.41 (s, 1H), 8.01(dd, J = 8.8 Hz, J = 0.8 Hz, 1H), 7.80-7.67 (m,
3H),7.65-7.61 (m, 5H), 7.44-7.40 (m, 1H), 7.31 (d, J = 8.0 Hz, 2H), 2.35 (s, 3H) ppm; 13C NMR (100.6 MHz, DMSO-
d6): δ 172.5, 153.6, 142.8, 139.9, 138.9, 134.3, 133.2, 130.4, 128.7, 127.8, 127.7, 125.7, 125.2, 124.9, 119.1, 118.4,
21.0 ppm. ESI-HRMS: m/z Calcd for C22H16ClNO3S+H+:410.0612, found 410.0616.
2-(4-bromophenyl)-3-tosylquinolin-4(1H)-one (3ga).White solid; (82.4 mg, 91%); mp: 281-285 oC; Rf = 0.35 (CH2Cl2 /
methanol 20:1); 1H NMR (400 MHz, DMSO-d6): δ = 12.41 (s, 1H), 8.01(dd, J = 8.0 Hz, J = 0.8 Hz, 1H), 7.80-7.72 (m,
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5H), 7.66-7.59 (m, 3H),7.44-7.40 (m, 1H), 7.31 (d, J = 8.0 Hz, 2H), 2.35 (s, 3H) ppm; 13C NMR (100.6 MHz, DMSO-
d6): δ 172.5, 153.6, 142.8, 139.9, 138.8, 133.5, 133.3, 130.6, 128.7, 127.8, 125.7, 125.3, 124.9, 123.1, 119.0, 118.4,
21.0 ppm. ESI-HRMS: m/z Calcd for C22H16BrNO3S+H+:454.0107, found 454.0110.
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2-(4-ethylphenyl)-3-tosylquinolin-4(1H)-one (3ha).White solid; (71.6 mg, 92%); mp: 266-269 C; Rf = 0.37 (CH2Cl2 /
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methanol 20:1); H NMR (400 MHz, DMSO-d6): δ = 12.32 (s, 1H), 7.99 (dd, J = 8.0 Hz, J = 1.2 Hz, 1H), 7.78-7.67
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(m, 4H), 7.53 (d, J = 8.0 Hz, 2H), 7.43-7.39 (m, 3H), 7.31 (d, J = 8.0 Hz, 2H), 2.73 (q, J = 7.6 Hz, 2H), 2.35 (s, 3H),
1.26 (t, J = 7.6 Hz, 2H) ppm; 13C NMR (100.6 MHz, DMSO-d6): δ 172.5, 154.9, 145.3, 142.6, 140.2, 138.8, 133.2,
131.7, 128.7, 128.5, 127.7, 127.1, 125.1, 124.9, 119.0, 118.4, 28.1, 21.0, 15.6 ppm. ESI-HRMS: m/z Calcd for
C24H21NO3S+H+:404.1315, found 404.1318
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2-([1,1'-biphenyl]-4-yl)-3-tosylquinolin-4(1H)-one (3ia).White solid; (84.8 mg, 94%); mp: 282-286 C; Rf = 0.36
(CH2Cl2 / methanol 20:1); 1H NMR (400 MHz, DMSO-d6): δ = 12.43 (s, 1H), 8.02 (d, J = 8.0 Hz, 1H), 7.88-7.86 (m,
2H), 7.83-7.77(m, 4H), 7.75-7.69 (m, 4H),7.56-7.52 (m, 2H), 7.45-7.41 (m, 2H),7.33 (d, J = 8.0 Hz, 2H), 2.36 (s, 3H)
ppm; 13C NMR (100.6 MHz, DMSO-d6): δ 172.5, 154.5, 142.7, 141.2, 140.1, 139.4, 138.8, 133.4, 133.2, 129.1, 128.7,
127.9, 127.7, 127.1, 126.8, 125.9, 125.6, 125.2, 124.9, 119.0, 118.4, 21.0 ppm. ESI-HRMS: m/z Calcd for
C28H21NO3S+H+:452.1315, found 452.1318.
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6-chloro-2-phenyl-3-tosylquinolin-4(1H)-one (3ja).White solid; (80.6 mg, 89%); mp: 269-274 C; Rf = 0.35 (CH2Cl2 /
methanol 20:1);1H NMR (400 MHz, DMSO-d6): δ = 12.52(s, 1H), 7.78 (d, J = 8.4 Hz, 2H), 7.72 (d, J = 8.8 Hz, 1H),
7.65-7.63 (m, 3H), 7.57-7.54(m, 3H), 7.49-7.46 (m, 1H), 7.32 (d, J = 8.0 Hz, 2H), 2.36 (s, 3H) ppm; 13C NMR (100.6
MHz, DMSO-d6): δ 172.1, 155.2, 142.8, 139.9, 139.7, 134.0, 129.7, 128.7, 128.4, 128.2, 128.0, 127.7, 127.2, 126.5,
125.5, 121.3, 119.0, 21.0 ppm. ESI-HRMS: m/z Calcd for C22H16ClNO3S+H+:410.0612, found 410.0615.
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6-bromo-2-phenyl-3-tosylquinolin-4(1H)-one (3ka).White solid; (88.5 mg, 91%); mp: 288-292 C; Rf = 0.37 (CH2Cl2 /
methanol 20:1); 1H NMR (400 MHz, DMSO-d6): δ = 12.54 (s, 1H), 8.09 (d, J = 1.8 Hz, 1H), 7.90 (dd, J = 8.8 Hz, J =
1.8 Hz, 1H), 7.78 (d, J = 8.4 Hz, 2H), 7.66-7.63 (m, 3H), 7.59-7.56 (m, 3H), 7.32 (d, J = 8.0 Hz, 2H), 2.36 (s, 3H)
ppm; 13C NMR (100.6 MHz, DMSO-d6): δ 172.5, 153.8, 142.7, 140.0, 138.7, 133.2, 130.9, 130.8, 128.7, 127.7, 125.7,
125.2, 124.9, 119.0, 118.5, 114.8, 114.6, 21.0 ppm. ESI-HRMS: m/z Calcd for C22H16BrNO3S+H+:454.0107, found
454.0104.
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7-bromo-2-phenyl-3-tosylquinolin-4(1H)-one (3la).White solid; (76.1 mg, 93%); mp: 272-274 C; Rf = 0.35 (CH2Cl2 /
methanol 20:1); 1H NMR (400 MHz, DMSO-d6): δ = 12.38 (s, 1H), 7.92 (d, J = 8.4 Hz, 1H), 7.85 (d, J = 1.6 Hz, 1H),
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7.78 (d, J = 8.0 Hz, 2H), 7.64-7.62 (m, 2H), 7.59-7.55 (m, 4H), 7.32 (d, J = 8.0 Hz, 2H), 2.35 (s, 3H) ppm; 13C NMR
(100.6 MHz, DMSO-d6): δ 171.6, 154.3, 142.7, 140.0, 136.8, 136.0, 134.1, 129.6, 129.3, 128.7, 128.5, 127.8, 127.7,
126.9, 125.2, 121.3, 113.4, 21.0 ppm. ESI-HRMS: m/z Calcd for C22H16BrNO3S+H+:454.0107, found 454.0110.
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7-bromo-2-(4-chlorophenyl)-3-tosylquinolin-4(1H)-one (3ma).White solid; (78.8 mg, 87%); mp: 265-269 oC; Rf = 0.37
(CH2Cl2 / methanol 20:1); 1H NMR (400 MHz, DMSO-d6): δ = 12.42 (s, 1H), 7.92 (d, J =8.4 Hz, 1H), 7.82 (d, J = 2.0
Hz, 1H), 7.81 (d, J = 11.6 Hz, 2H), 7.77-7.63 (m, 4H), 7.59-7.56 (m, 1H), 7.32 (d, J = 8.0 Hz, 2H), 2.35 (s, 3H) ppm;
13C NMR (100.6 MHz, DMSO-d6): δ 171.3, 155.0, 142.8, 139.8, 137.8, 136.0, 134.0, 129.6, 128.7, 128.4, 127.8,
127.7, 127.0, 121.6, 118.9, 117.9, 21.0 ppm. ESI-HRMS: m/z Calcd for C22H15BrClNO3S+H+:487.9717, found
487.9714.
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2-(thiophen-2-yl)-3-tosylquinolin-4(1H)-one (3na).White solid; (73.2 mg, 96%); mp: 252-256 C; Rf = 0.44 (CH2Cl2 /
methanol 20:1); 1H NMR (400 MHz, DMSO-d6): δ = 12.53 (s, 1H), 7.99 (d, J = 8.0 Hz, 1H), 7.90 (dd, J = 5.2 Hz, J =
1.2 Hz, 1H), 7.81 (d, J = 8.4 Hz, 2H), 7.77-7.67 (m, 2H), 7.51 (dd, J = 5.2 Hz, J = 1.2 Hz, 1H),7.44-7.40 (m, 1H), 7.32
(d, J = 8.0 Hz, 2H), 7.25 (dd, J = 5.2 Hz, J = 3.6 Hz, 1H), 2.36 (s, 3H) ppm; 13C NMR (100.6 MHz, DMSO-d6): δ
172.4, 147.8, 142.8, 140.0, 138.7, 133.4, 132.8, 130.3, 129.0, 128.7, 126.8, 125.8, 125.4, 124.9, 119.8, 119.1, 21.0
ppm. ESI-HRMS: m/z Calcd for C20H15NO3S2+H+:382.0566, found 382.0568.
2-phenyl-3-(phenylsulfonyl)quinolin-4(1H)-one (3ab).White solid; (63.5 mg, 88%); mp: 262-266 oC; Rf = 0.42 (CH2Cl2
/ methanol 20:1); 1H NMR (400 MHz, DMSO-d6): δ = 12.41 (s, 1H), 8.01 (d, J = 8.0 Hz, 1H), 7.91 (d, J = 7.6 Hz, 2H),
7.76-7.70 (m, 2H), 7.68 -7.64(m, 2H),7.61-7.42 (m, 6H), 7.40 (t, J = 7.6 Hz, 1H) ppm; 13C NMR (100.6 MHz, DMSO-
d6): δ 172.6, 154.9, 142.9, 138.8, 134.2, 133.3, 132.4, 129.5, 128.4, 128.3, 127.7, 127.5, 125.6, 125.2, 124.9, 119.1,
118.1 ppm. ESI-HRMS: m/z Calcd for C21H15NO3S+H+:362.0845, found 362.0848.
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3-((4-bromophenyl)sulfonyl)-2-phenylquinolin-4(1H)-one (3ac).White solid; (76.2 mg, 87%); mp: 276-278 C; Rf =
1
0.43 (CH2Cl2 / methanol 20:1); H NMR (400 MHz, DMSO-d6): δ = 12.49 (s, 1H), 8.01 (dd, J = 8.0 Hz, J = 1.2 Hz,
1H), 7.82 (d, J = 8.8 Hz, 2H), 7.78-7.70 (m, 4H), 7.66-7.64 (m, 2H), 7.59-7.54 (m, 3H), 7.46-7.42 (m, 1H) ppm; 13C
NMR (100.6 MHz, DMSO-d6): δ 172.6, 155.1, 142.2, 138.8, 134.0, 133.4, 131.4, 129.7, 128.5, 127.7, 126.3, 125.6,
125.4, 124.9, 119.1, 117.7 ppm. ESI-HRMS: m/z Calcd for C21H14BrNO3S+H+:439.9951, found 439.9948.
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3-((2-bromophenyl)sulfonyl)-2-phenylquinolin-4(1H)-one (3ad).White solid; (58.7 mg, 67%); mp: 272-276 C; Rf =
1
0.42 (CH2Cl2 / methanol 20:1); H NMR (400 MHz, DMSO-d6): δ = 12.54 (s, 1H), 8.21 (dd, J = 8.0 Hz, J = 1.2 Hz,
1H), 7.96 (d, J = 7.6 Hz, 1H), 7.79-7.73 (m, 2H), 7.69 (dd, J = 7.6 Hz, J = 1.6 Hz, 2H), 7.62-7.42 (m, 5H), 7.41 (dd, J
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= 6.0 Hz, J = 2.0 Hz, 2H) ppm; 13C NMR (100.6 MHz, DMSO-d6): δ 172.1, 155.8, 141.7, 138.9, 134.4, 133.7, 133.3,
131.7, 130.0, 129.0, 127.8, 127.4, 125.3, 125.2, 124.9, 119.2, 118.5, 117.2 ppm. ESI-HRMS: m/z Calcd for
C21H14BrNO3S+H+:439.9951, found 439.9948.
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3-((4-methoxyphenyl)sulfonyl)-2-phenylquinolin-4(1H)-one (3ae).White solid; (71.2 mg, 91%); mp: 278-281 C; Rf =
1
0.45 (CH2Cl2 / methanol 20:1); H NMR (400 MHz, DMSO-d6): δ = 12.35 (s, 1H), 8.03 (dd, J = 8.0 Hz, J = 0.8 Hz,
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1H), 7.85-7.83 (m, 2H), 7.76-7.67 (m, 2H), 7.63-7.61 (m, 2H), 7.58-7.55 (m, 3H), 7.44-7.40 (m, 1H), 7.05-7.02 (m,
2H) ppm; 13C NMR (100.6 MHz, DMSO-d6): δ 172.5, 162.3, 154.4, 138.8, 134.5, 134.2, 133.2, 130.1, 129.4, 128.4,
125.1, 124.9, 119.0, 118.9, 113.4, 55.6 ppm. ESI-HRMS: m/z Calcd for C22H17NO4S+H+:392.0951, found 392.0954.
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3-((4-(tert-butyl)phenyl)sulfonyl)-2-phenylquinolin-4(1H)-one (3af).White solid; (70.9 mg, 86%); mp: 267-270 C; Rf
= 0.47 (CH2Cl2 / methanol 20:1); 1H NMR (400 MHz, DMSO-d6): δ = 12.38 (s, 1H), 8.03 (dd, J = 8.0 Hz, J = 0.8 Hz,
1H), 7.84 (d, J = 8.4 Hz, 2H), 7.76-7.67 (m, 2H), 7.64-7.62 (m, 2H),7.58-7.53 (m, 5H), 7.44-7.40 (m, 1H) ppm; 13C
NMR (100.6 MHz, DMSO-d6): δ 172.6, 155.3, 154.8, 140.1, 138.8, 134.3, 133.2, 129.4, 128.4, 127.64, 127.60, 125.6,
125.2, 125.1, 124.9, 119.0, 118.3, 34.8, 30.8 ppm. ESI-HRMS: m/z Calcd for C25H23NO3S+H+:418.1471, found
418.1476.
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3-(naphthalen-2-ylsulfonyl)-2-phenylquinolin-4(1H)-one (3ag).White solid; (68.2 mg, 83%); mp: 265-269 C; Rf =
1
0.51(CH2Cl2 / methanol 20:1); H NMR (400 MHz, DMSO-d6): δ = 12.46 (s, 1H), 8.56 (s, 1H), 8.17-8.15 (d, J = 7.6
Hz, 1H), 8.03-7.96 (m, 3H), 7.86 (dd, J = 8.4 Hz, J = 1.6 Hz, 1H), 7.75-7.59 (m, 9H), 7.41-7.37 (m, 1H) ppm; 13C
NMR (100.6 MHz, DMSO-d6): δ 172.6, 155.1, 154.8, 140.1, 138.8, 134.3, 134.2, 133.3, 131.4, 129.6, 129.3, 128.60,
128.56, 128.1, 127.7, 127.2, 125.6, 125.2, 124.8, 123.1, 119.1, 118.0 ppm. ESI-HRMS: m/z Calcd for
C25H17NO3S+H+:412.1002, found 412.1006.
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1-methyl-2-phenyl-3-tosylquinolin-4(1H)-one (4). White solid; (66.9 mg, 86%); mp: 255-257 C; Rf = 0.36 (CH2Cl2 /
methanol 20:1); 1H NMR (400 MHz, CDCl3): δ = 8.41 (d, J = 1.2 Hz, 1H), 8.39 (d, J = 1.6 Hz, 2H), 7.91-7.69 (m, 1H),
7.59-7.58 (m, 3H), 7.54 (d, J = 8.8 Hz, 1H), 7.45-7.39 (m, 3H), 7.22 (d, J = 8.0 Hz, 2H), 3.43 (s, 3H), 2.36 (s, 3H)
ppm; 13C NMR (100.6 MHz, CDCl3): δ 173.1, 156.6, 143.1, 140.8, 139.9, 133.4, 133.3, 129.9, 128.8, 128.6, 128.3,
128.1, 127.7, 127.1, 125.4, 121.9, 116.5, 37.4, 21.5 ppm. ESI-HRMS: m/z Calcd for C23H19NO3S+H+: 390.1158, found
390.1156.
ACKNOWLEDGMENT
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We gratefully acknowledge the National Natural Science Foundation of China (21172106, 21174061, 21474048,
21372114 and 21672099).
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Supporting Information:
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1H, 19F and 13C NMR spectra of compounds 1a-1p, 3ba-3na, 3aa-3ag. X-ray crystal structure of 3fa. This material is
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available free of charge via the Internet at http://pubs.acs.org.
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